Gas chromatography-mass spectrometric studies of dihydrolipoyl dehydrogenase deficiency

Abstract

Using gas chromatography-mass spectrometry, urinary metabolic profile studies were carried out on a patient suspected of having MSUD by the Guthrie test. The urinary levels of lactate and 2-oxoglutarate during a clinical episode at seven months of age were extremely high. The levels of 2-hydroxybutyrate, 2-hydroxyglutarate and 2-hydroxymethylbutyrate were also elevated. Significant amounts of 2-hydroxyisovalerate, 2-hydroxyisocaproate and 2-oxoisocaproate were found. It was suggested that the patient has reduced but significant capability for branched-chain keto acid oxidation. After branched-chain amino acid restriction, 2-oxoglutarate levels were substantially lowered while lactate levels remained elevated. The lactate levels dramatically increased along with ketone bodies. From these data the patient was diagnosed as having a deficiency of dihydrolipoyl dehydrogenase (E3). THe usefulness of metabolic profile studies for rapid identification of E3 deficiency, prior to confirmatory enzyme studies, is discussed.